Herpes simplex is an infection caused by herpes hominis simplex Type I and II. The virus attacks the skin and/or mucous membranes before the lesion becomes visible. The first signs consist of mild parasthesia, burning sensation and itching or pain locally. Once the lesions develop, headaches, general malaise and low grade fever are common. This is followed by the appearance of small red papules that soon change to fluid filled blisters on the skin or mucous membranes which dry out within several weeks, scab and heal but tend to recur over and over again.
There are two types of herpes simplex. Type I is known as the skin or "above the umbilicus" virus that causes fever blisters, and type II is known as the "below the umbilicus" virus responsible for genital infections. The two types can be distinguished by serologic examination of the antibodies produced after exposure to the virus but cannot be differentiated in a culture. The herpes simplex infections are also named after their localisation, e.g., herpes labialis, occular herpes, herpes genitalis, rectal herpes, herpes digitalis, herpes progenitalis, herpes preputialis, intrauterine herpes, etc. They are aso called herpes febrilis, cold sores, or herpes menstrualis according to timing of their appearance with the above mentioned conditions. Both types of herpes, type I and II, can be sexually transmitted and cause lesions in and on the genitals, on thighs, buttocks, or in the mouth and rectum.
Herpes simplex virus can live for hours outside the human body on a variety of materials and surfaces including toilet seats, plastic containers, specula and gauze as reported by Larson and Bryson, Int. Med. News. 15: 17 (1982). It is actively infective for up to 21/2 months in dried crusts from herpetic lesions kept at room temperature as reported by Nahmias et al, "Transport Media for Herpes Simplex Virus Types I and II", Appl. Microbiol. 22: 451-454 (1971). Parvey and Chien, "Neonatal Herpes Virus Infection Introduced by Fetal-monitor Scalp Electrodes", Pediatrics 65: 1150-1153 (1980), described another possibility of non-sexual transmission of herpes simplex infection in an infant who developed acute herpes meningoencephalitis and pneumatosis intestinalis as a result of fetal monitoring with scalp electrodes on the buttocks. The first vesicles appeared at the site where the electrodes were placed. Montefiore et al, "Herpes Virus Hominis type II Infection in Ibadan, Problem of Non-Venereal Transmission", Br. J. Vener Dis. 56: 49-53 (1980), report a possibility of non-venereal transmission of herpes hominis type II that could survive for long enough on cloth samples under humid tropical conditions to cause infections. The herpes simplex hominis virus type I and II are members of a large herpes virus family of which about 70 varieties are known. Those harmful to humans cause birth defects, chicken pox, shingles, mononucleosis and are associated with malignant diseases.
Various treatment of herpes hominis simplex have been proposed. Asculai, U.S. Pat. No. 4,147,803, teaches that certain sorbitan derivatives have anti-herpetic activity. De Long et al., U.S. Pat. No. 3,639,612 described such activity for certain chalcogen containing heterocyclic compounds. Stedman, U.S. Pat. No. 3,555,355, discloses that certain cycloalkylamines have activity against herpes simplex. Fleming et al., U.S. Pat. No. 3,829,578, teaches that certain bis-basic ethers and xanthen-9-ones have anti-viral activity and Soichet, U.S. Pat. No. 4,312,884, describes such antiviral activity by Spectinomycin.
Kaufman et al, Arch. Ophthalmol. 68: 235-239 (1962), reported treatment of herpes simplex keratitis with 5-iodo-2-deoxyridine (IUD). Schabel describes treatment of genital herpetic infection with 9-beta-D-arabino-flurano-syladenine, Chemotherapy 13: 321-338 (1968), and reported antiviral activity of 5-trifluoromethyl-2-deoxyuridine, N.Y. Acad, Sci. 130: 168-180 (1965). Adams et al, J. Infect. Dis. 133 (suppl) 151-159 (1976), treated genital herpes infections with topical application of adenine arabinside. Felber et al, JAMA 223: 289-292 (1973), described treatment of herpes infections by application of a vital dye as neutral red or proflavine followed by exposure to light. Cheseman et al, N. Eng. J. Med. 300: 1345-1349 (1979), and Pazin et al, N. Engl. J. Med. 301: 225-230 (1979), report the treatment of herpes simplex infection by human leukocyte interferon. Blough and Giuntoli, JAMA 241: 2798-2801 (1979), described treatment of human genital herpes infections with 2-deoxy-D-glucose. Schaeffer et al, Nature 272: 583- 585 (1978), Fyfe et al, J. Biol. Chem. 253: 8721-8727 (1978), Selby et al, Lancet 2: 1267-1270 (1979), Park et al, J. Infect. Dis. 140: 802-806 (1979), and Pavan-Langston et al, Am. J. Ophthalmol. 86: 618-623 (1978), reported treatment of herpes infections by 9-(2-hydroxyethoxymethyl)guanine (Acyclovir). Fisher, Cutis 29: 467-472 (1982), described treatment of herpes simplex infections with Amantadine hydrochloride. Other forms of treatment of herpes hominis simplex Type I and II include a variety of agents such as lysine, ascorbic acid, topical ether and topical chloroform, tymol, nonionic surfactants, inactivated herpes viruses, zinc, urea, tannic acid, glutaraldehyde, cow pox vaccine, intradermal injections of gamma globulins, and a surgical treatment by epidermal excisions of the herpetic lesions.
It is the object of this invention to provide a new method of treatment and prophylaxis of infections by herpes simplex and related viruses. This and other objects of the invention will become apparent from the following description thereof.